Obesity is a common medical disorder which greatly increases the risk of life-threatening conditions such as high blood pressure and diabetes. The precise cause of obesity is not known, and current treatment methods have little or no success:
Recently, a gene was discovered, that, when mutated, caused severe hereditary obesity. The obesity gene (Ob gene) has been demonstrated to encode a protein, now termed leptin, which controls food intake and energy metabolism.
Leptin is primarily secreted by adipose tissue, and exerts its effects by interactions with specific receptors, e.g. in the hypothalamus. In humans, circulating leptin levels are increased in obesity and regulated by fasting, feeding, and body weight changes.
As described in the Examples below, it has now been found that the majority of circulating leptin in lean subjects with minimal adipose tissue is bound to a binding protein, whereas in obese subjects, the majority of leptin circulates as free leptin.
Modulating binding protein systems exist for circulating hormones and factors including steroid and thyroid hormones and growth factors such as insulin-like growth factor. Specific leptin binding proteins in blood could serve to modulate the active form leptin. Thus, there is a need to isolate and provide a leptin binding protein that could effectively modulate levels of bound and free leptin in circulation.